| Background:The central nervous system infection (CNSI) is a kind of etiology clear, inflammatory disease caused by pathogenic microorganism in the nervous system. It is one of the common disease in neurology, especially in patients with craniocerebral surgery. It has high mortality and morbidity, so it is important to be diagnosed early and be treated timely to improve the long-term prognosis of the patients. However, follow-up the development of clinical diagnosis and treatment technology, new clinical cases makes diagnosis of the central nervous system infection difficult. On one hand, with the wide application of antibacterial drugs, a large number of patients with suspected infection, have been used for a large number of antibacterial drugs, which not only cover the clinical manifestations of central nervous system infection, moreover affect the reliability of laboratory results of the central nervous system infection, so it makes difficult to diagnose central nervous system infection. On the other hand, along with the development of neurology, all kinds of invasive treatments and brain implants and hemostatic materials applications, especially in patients with craniocerebral surgery, can cause foreign body reaction, which has the same clinical manifestations of central nervous system infection, such as fever and headache. So it also makes the early diagnosis of central nervous system infection very difficult. Laboratory examination plays an important role in the diagnosis and differential diagnosis of central nervous system infection. However, with the emergence of new clinical situation, the traditional laboratory test because of its shortcomings, far cannot meet the needs of current clinical diagnosis. Therefore, in view of the emergence of new clinical situation, looking for a more specific and sensitive laboratory detection method become a very pressing task.TNF alpha,which secreted by immune cells (macrophages) and other cells in the body tissue, has a broad range of biological activity in antitumor and anti-infection.In the central nervous system, the TNF alpha mainly secreted by macrophages. Besides, not only astrocytes, vascular endothelial cells and microglia can produce TNF alpha, neurons can also produce TNF alpha. When the brain tissue suffers from a variety of external stimulation, especially the stimulation of bacterial lipopolysaccharide, brain tissue can secrete a large number of TNF alpha, in order to resist invasion of pathogen. TNF alpha plays an important role in the early stage of infection. Through the researches of TNF alpha, it is found that when the tissue cells just only suffers by the pathogen itself or its Secretion, the tissue cells can secrete a large number of TNF alpha in the early stage of infection. And it is not affected by the application of antibiotics and invasive manipulation of the brain. So a lot researches have been achieved to prove that when the bacterial meningitis occurs, the level of TNF alpha in cerebrospinal fluid will significantly increase, but when the virus meningitis occurs, the level of TNF alpha in cerebrospinal fluid will not increase so much. However, the researches of TNF alpha about the diagnosis of brain infection have some questions, just like small sample size, different diagnosis of sensitivity and specificity and so on.So, this article aims to Comprehensively assess the researches of TNF alpha about the diagnosis of brain infection by Meta analysis, in order to provide theoretical basis for the clinical application and promotion.ObjectiveWe collected the literatures about the diagnostic value of CSF TNF alpha to identify bacterial meningitis and viral meningitis at home and abroad, and evaluated its diagnostic value with Meta analysis. Through that, it can provide a new way to diagnose central nervous system infection and identify causative agent. Besides it can also provide theoretical basis to guide the clinical applicationMethods and materialsThis study was conducted following the Meta-analysis of observational studies in epidemiology guidelines, simultaneously conforming to most of the preferred reporting items for systematic reviews and Meta-analyses guidelines.We performed an electronic search of PubMed, EMBASE, the Cochrane library, CBM, CNKI, VIP and Wanfang from inception of each database to September2012. We included studies if they met all the following criteria:(1)Object of the researches include two groups, one includes the patients with bacterial meningitis and the other includes the patients with viral meningitis;(2)It can be directly or indirectly to obtain all the diagnosis information of TNF alpha in cerebrospinal fluid,just like True-Positives, False-Positives, True-Negatives and False-Negatives;(3) It can be directly or indirectly to obtain the diagnosis of positive predictive value. We excluded studies if they met all the following criteria:(1) Object of the researches just only include one group;(2)It can not obtain the diagnosis information.The quality of included studies were assessed based on the Quality Assessment of Studies of Diagnostic Accuracy included in Systematic Reviews (QU ADAS) for quality of diagnostic studies in Meta-analyses. This article use the Meta-Disc1.4software for Meta analysis. We obtain the data such as True-Positives, False-Positives, True-Negatives and False-Negatives from all the researches, and draw the Summary receiver operating characteristic(SROC), in order to estimated the total diagnostic test accuracy. Through calculating Spearman correlation, X2and I2to evaluate whether there is heterogeneity, and then decide using which to do the Meta analysis, random effects model or fixed effect model. At the same time, we will do the Sensitivity analysis and subgroup analysis of the include researches.ResultsTwenty-one studies were included in our Meta-analysis involving558patients with bacterial meningitis and651patients with virus meningitis, including11english researches and10chinese researches, and14researches for the children,7researches for the adult. And13researches use the Elisa detection,6researches use radioimmunoassay,1research use immunochemiluminometric assays,1research use chemiluminescence.1. Results of quality evaluation of literatureAll studies included2kinds of disease, bacterial meningitis and viral meningitis. All patients received the same standard test. And no patient gives up from all the studies. Only5studies describe the standard of into and out of the test of the patients.4studies don’t describe the standard test. The test of TNF alpha with the standard test or control test is carried out at the same time. TNF alpha testing method in all studies can be repeated. In all, all studies included have good quality.2. Results of heterogeneity testSpearman correlation is0.049and P=0.834. It says that there is no threshold effect in all studies. Cochran-Q=31.93, P=0.0441<0.05, X2of merger of sensitivity is54.67,and I2=63.4%. X2of merger of specificity is48.87,and I2=59.1%. We cloud say that there has heterogeneity among the studies.3. Result of Meta-analyses3.1Risults of effectsizeThe information about TNF alpha to differential diagnosis bacterial meningitis and virus meningitis includes the following index:Sensitivity=0.80(95%CI:0.76to0.83),specificity=0.92(95%CI:0.89-0.94), likelihood ratio positive=.55(95%CI:5.26-10.83),likelihood ratio negative=0.26(95%CI:0.21-0.32) diagnostic odds ratio=38.52(95%CI:23.08-64.29) and the AUC of SROC=0.9267(SE=0.0132), Q*=0.8612(SE=0.0156).3.2Results of subgroup analysisAccording to the country (China or foreign country), age (children or adults), method of TNF alpha test, we divided all the studies into some groups. Through the subgroup analysis, we cloud know that there is no different between all the groups, no matter between Chinese and foreigners, or between children and adults.3.3Results of sensitivity analysis We removed the included studies one by one, and then do the Meta-analyses again. And we find that the AUC of Summary receiver operating characteristic (SROC) don’t change much. That is to say that the quality of all included studies is reliable.Conclusion1. TNF alpha in Cerebrospinal fluid has a highly accurate sensitivity and specificity with a strong ROC curve, which makes it a new marker to differentiate bacterial meningitis from viral meningitis.2. According to the results of subgroup analysis, we know that this way of diagnosis can be spreaded in all people, no matter Chinese or foreigners, children or adults. |
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